Combination product composed of pyrimido-pyrimidines and O-acetylsalicylic acid or its pharmacologically tolerated salts, and its use

Abstract

O-acetylsalicylic acid and a pyrimido-pyrimidine as combination products.

We claim: 
     
       1. A pharmaceutical combination composition containing as essential ingredients (A) hand a pyrimido-pyrimidine of the formula I ##STR2##  wherein at least one of the groups R 1  and R 3  represents the group --N(CH 2  --CHR 5  OH) 2  in which R 5  is hydrogen or methyl and at least one of the groups R 2  and R 4  is the group ##STR3##  or an effective metabolite or salt or combination thereof and (B) hand O-acetylsalicylic acid or a pharmaceutically tolerable salt thereof, the weight ratio between component (A) and component (B) being higher than 0.5 and at most 30, (C) together with or without a pharmaceutical carrier, for the consecutive application in the therapy of diseases which are caused or characterized by impaired blood functions or blood ingredients, such that component (A) is at first released.   
     
     
       2. A composition according to claim 1, wherein component (A) is present in the form of dipyridamol. 
     
     
       3. A composition according to claim 1, wherein the composition is present in the form of a dosage unit to be administered orally or rectally. 
     
     
       4. A composition according to claim 5, wherein the dosage unit contains from 10 to 150 mg dipyridamol and 10 to less than 300 mg acetylsalicyclic acid or an equivalent amount of a salt thereof. 
     
     
       5. A composition according to claim 4, wherein the dosage unit contains from 25 to 75 mg dipyridamol. 
     
     
       6. A composition according to claim 3, wherein the dosage unit contains from 10 to 660 mg of mopidamol and 10 to less than 1200 mg of acetylsalicylic acid or of an equialent amount of a salt thereof. 
     
     
       7. A composition according to claim 6, wherein the dosage unit contains from 200 to 250 mg of monipdamol. 
     
     
       8. A composition as claimed in claim 6, wherein the dosage unit contains from 100 to 500 mg of acetylsalicylic acid or of an equivalent amount of a salt thereof. 
     
     
       9. A composition according to claim 8, wherein the dosage unit contains from 200 to 250 mg of mopidamol. 
     
     
       10. A composition according to claim 1, wherein the upper limit for the weight ratio between component (A) and component (B) is at 10 and the lower limit is at 0.6. 
     
     
       11. A composition according to claim 10, wherein the upper limit is at 3. 
     
     
       12. A composition according to claim 1, wherein the carrier for the acetylsalicylic acid component (B) contains at least one agent providing a retarding action. 
     
     
       13. A composition according to claim 1, wherein the composition is present in the form of microcapsules, the material of the capsules containing the acetylsalicylic acid component being resistant towards gastric juice or providing a retarded release. 
     
     
       14. A composition according to claim 1, wherein the composition is present in the form of a laminated tablet or multi-layer tablet in which the pyrimidopyrimidine component (A) is contained in the layer first to be resorbed. 
     
     
       15. A method for the treatment of diseases which are caused by impaired blood functions or blood ingredients which comprises administering an effective amount of (A) a pyrimido-pyrimidine of the formula I as defined in claim 1 or an effective metabolite or salt or a combination thereof and (B) O-acetylsalicylic acid or a pharmaceutically tolerable salt thereof in a separate form simultaneously or consecutively in a time difference of 15 minutes to 2 hours such that the pyrimido-pyrimidine component (A) is released to the body prior to the acetylaslicyclic acid component (B) or such that the pyrimidio-pyrimdin component (A) is at first administered and the acetylsalicyclic acid component B is subsequently administered such that the acetylsalicyclic acid component (B) is released 15 minutes to 2 hours later than the pyrimido-pyrimidine component (A), to a human or animal recipient suffering from said diseases. 
     
     
       16. A method for the treatment of a disease which is caused by impaired blood functions or blood ingredients which comprises administering an effective amount of the pharmaceutical composition claimed in claim 1 to a human or animal recipient suffering from said diseaes, thus providing a consecutive release at first of component (A) and subsequently of component (B). 
     
     
       17. The method according to claim 16 for the treatment of a disease which is caused by impaired thrombocytes or erthrocytes. 
     
     
       18. A process for the manufacture of a pharmaceutical composition wherein (A) a pyrimido-pyrimidine of the formula I according to claim 1 or an effective metabolite or salt or a combination thereof and (B) O-acetylsalicyclic acid or a pharmaceutically tolerable salt thereof are processed per se or together with (C) a pharmaceutical carrier in a conventional manner to laminated tablets or multi-layer tablets or suppositories with the pyrimido-pyrimdine (A) in the outer layer and the component (B) in the core or the other layer in a form which is less soluble in gastric juice, but soluble in the intestinal juice, or wherein said components are combined in capsules, the weight ratio of component (A) to component (B) being higher than 0.5 and at most 30.